Clarification of mechanisms to regulate the activity of protein deacetylase SIRT1 and its therapeutic application in heart failure

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590869
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: TANNO Masaya Sapporo Medical University, 医学部, 助教 (00398322)
• Co-Investigator(Kenkyū-buntansha): MIURA Tetsuji 札幌医科大学, 医学部, 教授 (90199951) ; HORIO Yoshiyuki 札幌医科大学, 医学部, 教授 (30181530)
• Project Period (FY): 2008 – 2010
• Keywords: 分子心臓病態学 / 心不全 / エピジェネティクス

Research Abstract

SIRT1 shuttled between the nuclei and cytoplasm. Nuclear SIRT1 suppressed oxidative stress-induced cell death by up-regulating Mn-SOD. SIRT1 accumulated in nuclei in cardiomyocytes of failing hearts probably as an endogenous adaptive mechanism and activation of SIRT1 by resveratrol reduced the mortality in cardiomyopathic hamsters. These findings suggest that SIRT1 activator may be a novel therapeutic approach for chronic heart failure.

Research Products

• [Journal Article] Hypertensive hypertrophied myocardium is vulnerable to infarction and refractory to erythropoietin-induced protection. (2010)
  • Author(s): Yano T, Miki T, Tanno M, Kuno A, Itoh T, Takada A, Sato T, Kouzu H, Shimamoto K Miura T.
  • Journal Title: Hypertension 57 Pages: 110-115
  • Peer Reviewed
• [Journal Article] Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure (2010)
  • Author(s): Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K, Horio Y.
  • Journal Title: J Biol Chem 285 Pages: 8375-82
  • Peer Reviewed
• [Journal Article] Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells (2010)
  • Author(s): Sugino T, Maruyama M, Tanno M, Kuno A, Houkin K, Horio Y.
  • Journal Title: FEBS Lett 584 Pages: 2821-6
  • Peer Reviewed
• [Journal Article] Mitochondrial kinase signalling pathways in myocardial protection fromischaemia/reperfusion-induced necrosis (2010)
  • Author(s): Miura T, Tanno M, Sato T.
  • Journal Title: Cardiovasc Res 88 Pages: 7-15
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phospho-glycogen synthase kinase 3beta-mediated suppression of mitochondrial permeability transition (2009)
  • Author(s): Miki T, Miura T, Hotta H, Tanno M, Yano T, Sato T, Ishikawa S, Shimamoto K.
  • Journal Title: Diabetes 58 Pages: 2863-72
  • Peer Reviewed
• [Journal Article] Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation (2008)
  • Author(s): Hisahara S, Chiba S, Matsumoto H, Tanno M, Yagi H, Shimohama S, Horio Y.
  • Journal Title: Proc Natl Acad Sci U S A 105 Pages: 15599-15604
  • Peer Reviewed
• [Presentation] Activation of Sirt1 suppresses hypertrophic response of cardiomyocytes by inhibition of H3K9 acetylation via p roteasome-mediated p300 degradation. (2010)
  • Author(s): Kuno A, Tanno M, Ishikawa S, Horio Y, Miura T.
  • Organizer: 83^<rd> Scientific Session of American Heart Association
  • Place of Presentation: Chicago,U.S.A.
  • Year and Date: 20101113-20101117
• [Presentation] The SIRT1 activator resveratrol suppresses cardiomy ocyte hypertrophy by promoting histone H3 Lys9 deacetylation and tri-methylation. (2009)
  • Author(s): Kuno A, Tanno M, Yano T, Takada A, Miura T, Horio Y, Shimamoto K.
  • Organizer: 82^<nd> Scientific Session of American Heart Association
  • Place of Presentation: Orlando, U.S.A.
  • Year and Date: 20091114-20091118
• [Presentation] Activation of histone/protein deacetylase SIRT1 by resveratrol induces MnSOD up-regulation via FOXO3a and improves survival of heart failure animals. (2009)
  • Author(s): Kuno A, Tanno M, Miura T, Horio Y, Shimamoto K.
  • Organizer: 31^<st> Congress of the European Society of Cardiology
  • Place of Presentation: Barcelona,Spain
  • Year and Date: 20090829-20090902
• [Presentation] Activation of a protein deacetylase,SIRT1, by resveratrol suppresses progression of heart failure and improves survival by up-regulation of Mn-SOD. (2008)
  • Author(s): Tanno M, Kuno A, Miki T, Miura T, Horio Y, Shimamoto K.
  • Organizer: 81^<st> Scientific Session of American Heart Association
  • Place of Presentation: New Orleans, U.S.A.
  • Year and Date: 20081108-20081112
• [Presentation] Resveratrol, an activator of protein deacetylase SIRT1, suppresses oxidative stress-induced cell death by upregulating MnSOD expression through transactivation of FOXO3a . (2008)
  • Author(s): Kuno A, Tanno M, Miura T, Horio Y, Shimamoto K.
  • Organizer: 81^<st> Scientific Session of America n Heart Association
  • Place of Presentation: New Orleans,U.S.A.
  • Year and Date: 20081108-20081112